In ambient mass spectrometry, the performance in direct in situ analysis applications has been hindered by the lack of efficient ion-transferring technique between the atmosphere pressure ionization source and the mass analyzer. Building upon the hybrid concept of a stack ring ion guide and multipole ion guide, this study proposes the concept of a reconfigurable twisted dipole ion guide (TDIG) that enables flexible ion transfer between atmosphere and vacuum. Initially, theoretical and numerical studies were conducted to understand the basic ion confining principle of the twisted dipole ion guide, revealing its unique merits in long-distance flexible ion transmission. The gas dynamics and ion transport performance of the TDIG are then evaluated by using computational fluid dynamics and ion trajectory simulation. To actualize the concept, specialized insulation brackets were designed based on the universal joint mechanism, and a practical twisted dipole ion guide prototype was built. The prototype was tested on a homemade nano electrospray ionization-time-of-flight-mass spectrometry (ESI-TOF-MS) platform. The results suggest that it is competent in flexible ion transfer and may serve as a versatile tool in ambient mass spectrometry. This innovation can potentially advance the development of in situ analytical mass spectrometry techniques.